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81.
Willingham SB Volkmer JP Gentles AJ Sahoo D Dalerba P Mitra SS Wang J Contreras-Trujillo H Martin R Cohen JD Lovelace P Scheeren FA Chao MP Weiskopf K Tang C Volkmer AK Naik TJ Storm TA Mosley AR Edris B Schmid SM Sun CK Chua MS Murillo O Rajendran P Cha AC Chin RK Kim D Adorno M Raveh T Tseng D Jaiswal S Enger PØ Steinberg GK Li G So SK Majeti R Harsh GR van de Rijn M Teng NN Sunwoo JB Alizadeh AA Clarke MF Weissman IL 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(17):6662-6667
CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies. 相似文献
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Eliú Elgorriaga-Islas Piero Guggiana-Nilo Mariana Domínguez-Yévenes Gerardo González-Rocha Sergio Mella-Montecinos Jaime Labarca-Labarca Patricia García-Cañete Helia Bello-Toledo 《Enfermedades infecciosas y microbiología clínica》2012
Introduction
The frequency of aac(6′)-Ib-cr gene in ESBL-producing strains of Klebsiella pneumoniae and Escherichia coli is unknown, in Chile.Methodology
The aac(6′)-Ib and aac(6’)-Ib-cr genes were investigated using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and sequencing, in strains isolated from 10 Chilean hospitals between 2008-2009.Results
The aac(6’)-Ib-cr gene was detected in 54% of K. pneumoniae and 74% of E. coli strains. The CIM50 of CIP was higher among strains harboring aac(6’)-Ib-cr, 8 times higher in K. pneumoniae and 4 times higher in E. coli. Moreover, both aac(6’)-Ib and aac(6’)-Ib-cr were simultaneously found in 13 K. pneumoniae and 3 E. coli isolates.Conclusion
This is the first report of aac(6’)-Ib-cr in ESBL-producing strains of K. pneumoniae and E. coli isolated from in-patients in Chilean hospitals located along an area of more than 2,800 Km. 相似文献85.
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With almost 100 years of clinical experience, antiepileptic drugs (AEDs) remain the mainstay of epilepsy treatment. They suppress epileptic seizures by acting on a variety of mechanisms and molecular targets involved in the regulation of neuronal excitability. These include inhibitory-GABAergic and excitatory-glutamatergic neurotransmission, as well as ion (sodium and calcium) conductance through voltage-gated channels. On the other hand, accruing evidence indicates that these mechanisms and targets are also implicated in the regulation of mood and behavior, which may explain why each AED is associated with specific psychotropic effects. These effects, however, cannot be explained solely on the basis of the known mode of action of each AED, and other mechanisms or targets are likely to be implicated. In this article, we review positive and negative effects of AEDs on mood and behavior, discuss putative underlying mechanisms, and highlight knowledge gaps which should be addressed in future studies.This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”. 相似文献
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Amodio P Salari L Montagnese S Schiff S Neri D Bianco T Minazzato L 《World journal of gastroenterology : WJG》2012,18(19):2295-2299
Hepatitis C virus (HCV) hepatitis and other diseases related to HCV, such as cryoglobulinemia, lymphoma and renal failure, impair health-related quality of life (HRQoL). In addition, HCV per se might directly influence HRQoL via colonization of microglia in the brain or, indirectly, via the effect of systemic inflammatory cytokines which, in turn, can trigger brain interleukin production. The treatment of HCV-related disorders with interferon (IFN) has an effect on HRQoL. Initially, IFN causes a transient deterioration of HRQoL, due to the induction of depression and other side effects of treatment. Subsequently, the subjects who obtain a sustained virologic response experience an improvement in HRQoL. Only rarely does interferon treatment causes permanent detrimental effects on HRQoL, due to residual psychiatric or neurologic side effects. Liver transplantation is the only treatment for end-stage HCV-related liver disease. HRQoL generally improves massively a few months after transplantation, except in the case of serious complications of the transplant procedure. Furthermore, high levels of anxiety and neuroticism pre-transplant are associated with lower HRQoL one year after transplant. Additionally, six months after transplant, patients with HCV who experience virologic recurrence show significantly greater depression, anxiety, phobic anxiety, and paranoid ideation than anti-HCV-negative patients. In conclusion, optimal care for the overall well-being of patients with HCV infection requires adequate knowledge of their neurological and psychological status. 相似文献
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Sara Montagnese Sami Schiff Matteo Turco Carlo Alberto Bonato Lorenzo Ridola Angelo Gatta Jean-Baptiste Nousbaum Oliviero Riggio Carlo Merkel Piero Amodio 《Digestive and liver disease》2012,44(11):957-960